Automated design and high throughput chemical synthesis of siRNA

The application of RNA interference (RNAi) to mammalian cells (Caplen et al., 2001; Elbashir et al., 2001a) has the potential to revolutionize the field of functional genomics and target validation in drug discovery research (Harborth et al., 2001; Tuschl and Borkhardt, 2002). In addition RNAi is also viewed as potential means for nucleic acid-based therapeutic applications. The ability to simply, effectively, and specifically down-regulate the expression of genes in mammalian cells holds enormous scientific, commercial, and therapeutic potential. To ensure success in gene silencing experiments, the design and synthesis of the targeting molecule (the siRNA) must be carefully optimized. The present chapter describes the design criteria for successful gene silencing, followed by a description of recent improvements in high-throughput chemical synthesis of siRNAs, and transcriptome wide gene silencing studies.